Plasma A beta 42/40 ratio alone or combined with FDG-PET can accurately predict amyloid-PET positivity: a cross-sectional analysis from the AB255 Study
Por:
Perez-Grijalba, V, Arbizu, J, Romero, J, Prieto, E, Pesini, P, Sarasa, L, Guillen, F, Monleon, I, San-Jose, I, Martinez-Lage, P, Munuera, J, Hernandez, I, Buendia, M, Sotolongo-Grau, O, Alegret, M, Ruiz, A, Tarraga, L, Boada, M, Sarasa, M, Goni, M, Pujadas, F, Villarejo, A, Frank, A, Pena-Casanova, J, Fernandez, M, Pinol, G, Blesa, R, Gil, P, Pascual, LF, Aguilar, M, Frisoni, GB, Matias-Guiu, J, Andreasen, N, Antunez, C
Publicada:
1 dic 2019
Resumen:
Background To facilitate population screening and clinical trials of disease-modifying therapies for Alzheimer's disease, supportive biomarker information is necessary. This study was aimed to investigate the association of plasma amyloid-beta (A beta) levels with the presence of pathological accumulation of A beta in the brain measured by amyloid-PET. Both plasma A beta 42/40 ratio alone or combined with an FDG-PET-based biomarker of neurodegeneration were assessed as potential AD biomarkers. Methods We included 39 cognitively normal subjects and 20 patients with mild cognitive impairment from the AB255 Study who had undergone PiB-PET scans. Total A beta 40 and A beta 42 levels in plasma (TP42/40) were quantified using ABtest kits. Subjects were dichotomized as A beta-PET positive or negative, and the ability of TP42/40 to detect A beta-PET positivity was assessed by logistic regression and receiver operating characteristic analyses. Combination of plasma A beta biomarkers and FDG-PET was further assessed as an improvement for brain amyloidosis detection and diagnosis classification. Results Eighteen (30.5%) subjects were A beta-PET positive. TP42/40 ratio alone identified A beta-PET status with an area under the curve (AUC) of 0.881 (95% confidence interval [CI] = 0.779-0.982). Discriminating performance of TP42/40 to detect A beta-PET-positive subjects yielded sensitivity and specificity values at Youden's cutoff of 77.8% and 87.5%, respectively, with a positive predictive value of 0.732 and negative predictive value of 0.900. All these parameters improved after adjusting the model for significant covariates. Applying TP42/40 as the first screening tool in a sequential diagnostic work-up would reduce the number of A beta-PET scans by 64%. Combination of both FDG-PET scores and plasma A beta biomarkers was found to be the most accurate A beta-PET predictor, with an AUC of 0.965 (95% CI = 0.913-0.100). Conclusions Plasma TP42/40 ratio showed a relevant and significant potential as a screening tool to identify brain A beta positivity in preclinical and prodromal stages of Alzheimer's disease.
Filiaciones:
Perez-Grijalba, V:
Araclon Biotech SL, Via Hispanidad 21, Zaragoza 50009, Spain
Arbizu, J:
Clin Univ Navarra, Serv Med Nucl, Pamplona, Spain
Romero, J:
Araclon Biotech SL, Via Hispanidad 21, Zaragoza 50009, Spain
Prieto, E:
Clin Univ Navarra, Serv Med Nucl, Pamplona, Spain
Pesini, P:
Araclon Biotech SL, Via Hispanidad 21, Zaragoza 50009, Spain
Sarasa, L:
Araclon Biotech SL, Via Hispanidad 21, Zaragoza 50009, Spain
Guillen, F:
Clin Univ Navarra, Serv Med Nucl, Pamplona, Spain
Monleon, I:
Araclon Biotech SL, Via Hispanidad 21, Zaragoza 50009, Spain
San-Jose, I:
Araclon Biotech SL, Via Hispanidad 21, Zaragoza 50009, Spain
Martinez-Lage, P:
Fdn CITA Alzheimer, Ctr Res & Adv Therapies, San Sebastian, Spain
Fdn CITA Alzheimer, Memory Clin, San Sebastian, Spain
Munuera, J:
Hosp Infantil St Joan Deu, Inst Recerca St Joan Deu, Barcelona, Spain
Hernandez, I:
Univ Int Catalunya Barcelona, Inst Catala Neurociencies Aplicades, Fundacio ACE, Res Ctr, Barcelona, Spain
Univ Int Catalunya Barcelona, Inst Catala Neurociencies Aplicades, Fundacio ACE, Memory Clin, Barcelona, Spain
Inst Salud Carlos III, Networking Res Ctr Neurodegenerat Dis CIBERNED, Madrid, Spain
Buendia, M:
Univ Int Catalunya Barcelona, Inst Catala Neurociencies Aplicades, Fundacio ACE, Res Ctr, Barcelona, Spain
Univ Int Catalunya Barcelona, Inst Catala Neurociencies Aplicades, Fundacio ACE, Memory Clin, Barcelona, Spain
Sotolongo-Grau, O:
Univ Int Catalunya Barcelona, Inst Catala Neurociencies Aplicades, Fundacio ACE, Res Ctr, Barcelona, Spain
Univ Int Catalunya Barcelona, Inst Catala Neurociencies Aplicades, Fundacio ACE, Memory Clin, Barcelona, Spain
Alegret, M:
Univ Int Catalunya Barcelona, Inst Catala Neurociencies Aplicades, Fundacio ACE, Res Ctr, Barcelona, Spain
Univ Int Catalunya Barcelona, Inst Catala Neurociencies Aplicades, Fundacio ACE, Memory Clin, Barcelona, Spain
Inst Salud Carlos III, Networking Res Ctr Neurodegenerat Dis CIBERNED, Madrid, Spain
Ruiz, A:
Univ Int Catalunya Barcelona, Inst Catala Neurociencies Aplicades, Fundacio ACE, Res Ctr, Barcelona, Spain
Univ Int Catalunya Barcelona, Inst Catala Neurociencies Aplicades, Fundacio ACE, Memory Clin, Barcelona, Spain
Inst Salud Carlos III, Networking Res Ctr Neurodegenerat Dis CIBERNED, Madrid, Spain
Tarraga, L:
Univ Int Catalunya Barcelona, Inst Catala Neurociencies Aplicades, Fundacio ACE, Res Ctr, Barcelona, Spain
Univ Int Catalunya Barcelona, Inst Catala Neurociencies Aplicades, Fundacio ACE, Memory Clin, Barcelona, Spain
Inst Salud Carlos III, Networking Res Ctr Neurodegenerat Dis CIBERNED, Madrid, Spain
Boada, M:
Univ Int Catalunya Barcelona, Inst Catala Neurociencies Aplicades, Fundacio ACE, Res Ctr, Barcelona, Spain
Univ Int Catalunya Barcelona, Inst Catala Neurociencies Aplicades, Fundacio ACE, Memory Clin, Barcelona, Spain
Inst Salud Carlos III, Networking Res Ctr Neurodegenerat Dis CIBERNED, Madrid, Spain
Sarasa, M:
Araclon Biotech SL, Via Hispanidad 21, Zaragoza 50009, Spain
Goni, M:
Hosp Divino Valles, Burgos, Spain
Pujadas, F:
Hosp Univ Vall dHebron, Barcelona, Spain
Villarejo, A:
Hosp Doce Octubre, Madrid, Spain
Frank, A:
Hosp La Paz, Madrid, Spain
Pena-Casanova, J:
Hosp Mar, Barcelona, Spain
Fernandez, M:
CAE Oroitu Algorta, Vizcaya, Spain
Pinol, G:
Hosp Santa Maria Lleida, Lleida, Spain
Blesa, R:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Gil, P:
Hosp Clin San Carlos, Madrid, Spain
Pascual, LF:
Hosp Lozano Blesa, Zaragoza, Spain
Aguilar, M:
Hosp Univ Mutua Terrassa, Terrassa, Spain
Frisoni, GB:
IRCCS Ctr San Giovanni di Dio FBF, Brescia, Italy
Matias-Guiu, J:
Hosp Clin San Carlos, Madrid, Spain
Andreasen, N:
Hosp Doce Octubre, Madrid, Spain
Antunez, C:
Fdn Alzheimur, Hosp Virgen Arrixaca, Murcia, Spain
Karolinska Inst, Stockholm, Sweden.
Green Published, gold
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